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dc.creatorQuinn, Connor
dc.creatorRico, Mario C.
dc.creatorMerali, Carmen
dc.creatorMerali, Salim
dc.date.accessioned2023-12-21T19:36:55Z
dc.date.available2023-12-21T19:36:55Z
dc.date.issued2022-02-11
dc.identifier.citationQuinn, C.; Rico, M.C.; Merali, C.; Merali, S. Dysregulation of S-adenosylmethionine Metabolism in Nonalcoholic Steatohepatitis Leads to Polyamine Flux and Oxidative Stress. Int. J. Mol. Sci. 2022, 23, 1986. https://doi.org/10.3390/ijms23041986
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/20.500.12613/9355
dc.description.abstractNonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease worldwide, with 25% of these patients developing nonalcoholic steatohepatitis (NASH). NASH significantly increases the risk of cirrhosis and decompensated liver failure. Past studies in rodent models have shown that glycine-N-methyltransferase (GNMT) knockout results in rapid steatosis, fibrosis, and hepatocellular carcinoma progression. However, the attenuation of GNMT in subjects with NASH and the molecular basis for its impact on the disease process is still unclear. To address this knowledge gap, we show the reduction of GNMT protein levels in the liver of NASH subjects compared to healthy controls. To gain insight into the impact of decreased GNMT in the disease process, we performed global label-free proteome studies on the livers from a murine modified amylin diet-based model of NASH. Histological and molecular characterization of the animal model demonstrate a high resemblance to human disease. We found that a reduction of GNMT leads to a significant increase in S-adenosylmethionine (AdoMet), an essential metabolite for transmethylation reactions and a substrate for polyamine synthesis. Further targeted proteomic and metabolomic studies demonstrated a decrease in GNMT transmethylation, increased flux through the polyamine pathway, and increased oxidative stress production contributing to NASH pathogenesis.
dc.format.extent14 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartInternational Journal of Molecular Sciences, Vol. 23, Iss. 4
dc.relation.isreferencedbyMDPI
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNonalcoholic steatohepatitis
dc.subjectPolyamines
dc.subjectGlycine-N-methyl transferase
dc.subjectS-adenosylmethionine
dc.titleDysregulation of S-adenosylmethionine Metabolism in Nonalcoholic Steatohepatitis Leads to Polyamine Flux and Oxidative Stress
dc.typeText
dc.type.genreJournal article
dc.description.departmentPharmaceutical Sciences
dc.relation.doihttp://dx.doi.org/10.3390/ijms23041986
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. School of Pharmacy
dc.creator.orcidMerali, Carmen|0000-0003-4679-710X
dc.creator.orcidMerali, Salim|0000-0002-0280-5289
dc.temple.creatorQuinn, Connor
dc.temple.creatorRico, Mario C.
dc.temple.creatorMerali, Carmen
dc.temple.creatorMerali, Salim
refterms.dateFOA2023-12-21T19:36:55Z


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